Capecitabine, Oxaliplatin, and Radiation Therapy in Treating Patients With Esophageal or Gastroesophageal Junction Cancer

Esophageal Cancer Clinical Trial

Official title:

A Phase II Study of Capecitabine and Oxaliplatin With Radiation for Esophageal and Gastroesophageal Junction Adenocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00711412
• Other study ID #: NU 05I2
• Secondary ID: STU00006779
• Status: Completed
• Phase: Phase 2
• Start date: May 31, 2006
• Est. completion date: January 30, 2013

Study information

• Verified date: July 2018
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as capecitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well giving capecitabine and oxaliplatin together with radiation therapy works in treating patients with esophageal or gastroesophageal junction cancer.

Description:

OBJECTIVES:

Primary

• Determine the pathologic complete response in patients with adenocarcinoma of the esophagus or gastroesophageal junction treated with neoadjuvant therapy comprising capecitabine, oxaliplatin, and radiotherapy.

Secondary

• Determine the clinical response rate in patients treated with this regimen.

• Determine the recurrence rate, time to progression, and patterns of failure in patients treated with this regimen.

• Characterize the toxicity profile of this regimen in these patients.

OUTLINE:

• Induction therapy: Patients receive oral capecitabine twice daily on days 1-14 and oxaliplatin IV over 2 hours on days 1 and 8. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

• Combination chemoradiotherapy: Patients then receive oxaliplatin IV over 2 hours once weekly for 6 weeks. Patients also receive concurrent oral capecitabine twice daily and undergo radiotherapy once daily 5 days a week for 5½ weeks in the absence of disease progression or unacceptable toxicity.

• Surgery: Patients undergo surgical resection at 4-8 weeks after completion of chemoradiotherapy.

After completion of study treatment, patients are followed every 3 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: January 30, 2013
• Est. primary completion date: May 29, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the esophagus or gastroesophageal junction

• Stage I-IVA disease

• No distant metastatic disease (other than regional lymph nodes)

• No evidence of CNS metastases

• CNS metastases stable for > 3 months allowed

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Consuming = 1,500 calories daily

• ANC = 1,500/mm³

• Platelet count = 100,000/mm³

• Bilirubin = 1.5 times upper limit of normal (ULN)

• SGOT = 2.5 times ULN

• Creatinine = 1.5 times ULN OR creatinine clearance = 50 mL/min

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No pre-existing neuropathy

• No prior unanticipated severe reaction to fluoropyrimidine therapy

• No known hypersensitivity to fluorouracil

• No known DPD deficiency

• No known hypersensitivity to any of the components of oxaliplatin

• No significant active infection or other severe complicated medical illness

• No clinically significant cardiac disease (e.g., congestive heart failure, symptomatic coronary artery disease, or cardiac arrhythmias not well controlled with medication)

• No myocardial infarction within the past 12 months

• No history of uncontrolled seizures, CNS disorders, or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake

• No malabsorption syndrome

• No other active malignancy within the past 3 years except cervical carcinoma in situ or nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

• More than 4 weeks since prior participation in any investigational drug study

• No prior pelvic or thoracic radiotherapy

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

Drug:
• Induction Therapy - Capecitabine
Two 21-day cycles will be given as induction. Capecitabine will be given at 1000 mg/m2 twice daily approximately 12 hours apart for 14 days, followed by seven days off.
• Induction Therapy - Oxaliplatin
Two 21-day cycles will be given as induction. Oxaliplatin will be given at 70 mg/m2 intravenously in 5% dextrose over two hours on days 1 and 8 of each cycle.
• Combination Therapy - Capecitabine
Two 21-day cycles will be given for combination therapy. Capecitabine will be given at 825 mg/m2 twice daily approximately 12 hours apart for five days (Monday through Friday) followed by two days off for 51/2 weeks.
• Combination Therapy - Oxaliplatin
Two 21-day cycles will be given. Oxaliplatin will be given at 50 mg/m2 intravenously in 5% dextrose over two hours on days 1, 8 and 15 of each cycle.

Radiation:
• Combination Therapy - Radiation
1.8 Gy daily Monday through Friday to a total of 50.4 Gy for 6 weeks during combination therapy.

Procedure:
• Evaluation for response and surgery
Four to eight weeks following the completion of therapy subjects will undergo evaluation for response and surgical resection.

Locations

Country	Name	City	State
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Northwestern University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine Pathologic Complete Response	Pathologic response will be assessed semiquantitatively irrespective of lymph node status based on the estimated percentage of residual carcinoma in relation total carcinoma area, including amount of radiotherapy-induced tissue injury, in mural histologic sections.; Pathologic response will be defined as: P0: 0% residual cancer P1: 1% to 50% residual cancer P2: more than 50% residual cancer	At time of surgery
Secondary	Clinical Response Rate	Clinical response Rate will be expressed as the proportion of patients demonstrating a complete and/or partial response based on all evaluable patients treated.Clinical response will be evaluated according to Response Evaluation Criteria In Solid Tumors 1.0 (RECIST) .; Complete Response (CR) is defined as the disappearance of all target lesions Partial Response (PR) is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions,taking as reference the baseline sum LD	four to six weeks following completion of 4 cycles (1 cycle = 21days) of chemotherapy treatment and prior to surgery
Secondary	Recurrence Rate	Recurrence rate will be defined as disease recurrence, progressive disease or death. Patients will be followed for disease recurrence or death until the end of the study.	From the time of start of treatment until first documentation of disease recurrence, progression or death, whichever comes first until the end of the study, a maximum of 6 years and 7 months.
Secondary	Time to Progression	Time to Progression will be measured as time from the first day of therapy until death, disease progression or last contact.	From start of first treatment until time of first documentation of progression of disease or death, whichever comes first, until the study closes, up to a maximum of 6 years and 7 months.
Secondary	Patterns of Failure		At time of surgery
Secondary	Toxicity Profile	Toxicity will be assessed at the beginning of every cycle during chemotherapy for a total of 4 cycles (1 cycle =21 days) and then 30 days post last dose of chemotherapy. All toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (CTCAE 3.0); In general adverse events (AEs) will be graded according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE; Only incidents of AEs determined to be related to chemotherapy are recorded here.	During chemotherapy treatment and up to 30 days post-last dose of chemotherapy.
Secondary	Correlate Proteomic and Pharmacologic Characteristics With Prognosis and Response to Therapy.		At time of sugery